The various cell types in a mammalian organism are often strikingly different from one another in structure and function. Nevertheless, they are all descendants of a single zygote formed by the fusion of an ovum with a sperm, and all the cells in a given organism are almost certainly genetically identical. The development and maintenance of cellular differences must therefore result from temporal and spatial control of gene expression. To approach this general problem, we propose in this application to study several specific aspects of gene regulation using approaches derived from genetics, cell biology and endocrinology. Specifically, we plan to investigate the mechanisms by which adrenal steroid hormones and other biological effectors regulate the expression of the tyrosine aminotransferase gene in cultured hepatoma cells. We shall also study the hormonal mechanisms which determine whether cells are in a rest, differentiated state or replicating in the cell cycle. These studies could contribute to an understanding both of the control of specific gene expression and also of the processes of development, malignant transformation, and hormone action.